1. Field of the Invention
The invention is directed to a device and method for providing radiation therapy, and more specifically, a device, system and method for providing shielded intracavitary brachytherapy (IB).
2. Related Art
For years, women with early stage breast cancers have had the option to choose breast conserving therapies (BCTs) over mastectomy. About 130,000 women are candidates for BCT in the U.S. annually. Until the mid 1990's, the only available BCT was lumpectomy, followed by external beam radiation therapy (EBRT) delivered to the whole breast in daily doses for 5-7 weeks. The combination of lumpectomy and EBRT has proven to be effective in preventing local recurrence of tumor. Despite BCT's success in fighting cancer, issues associated with scheduling 5-7 weeks of EBRT have prevented many from taking advantage of BCT. In some areas of the country, as few as 10% of medically eligible patients receive BCT. Moreover, whole breast irradiation is considered a significant contributor to adverse effects associated with this form of BCT.
Recently, methods for accelerated partial breast irradiation (APBI) have been developed, such as the technology for intracavitary brachytherapy (IB) of the breast marketed, for example, by Hologic, Inc., Cianna Medical, Xoft, Inc., and/or SenoRx, Inc. These allow patients to complete radiation treatment in 5 days. These also have better confined irradiation margins. The minimally invasive MammoSite Radiation Therapy System (MRTS) (such as marketed by Hologic, Inc.) appears to be the most widely used and fastest growing form of APBI.
MRTS works generally by implanting a small balloon into the cavity remaining after tumor removal. The balloon is inflated within the breast and then loaded with a tiny radioactive seed to deliver radiation from inside the breast directly to the tissue where cancer is most likely to recur, as well as farther from the skin where adverse reactions and cosmetic damage are dominant considerations.
If the skin-to-balloon distance is less then 7 mm, patients are not able to take advantage of MRTS. Studies show that this may affect as many as 4,000 patients each year. Small skin-to-balloon distances are associated with mild to acute adverse skin reactions, as in previous external beam therapies. These significantly impact the cosmetic outcome of BCT, which is a crucial consideration for patients undergoing breast preserving treatment.
Breast Conserving Therapy
Outcomes of multiple retrospective studies and randomized prospective trials have consistently demonstrated no significant differences between BCT and mastectomy in disease-free survival, distant disease-free survival and overall survival for an appropriately selected patient population. BCT typically involves breast-conserving surgery and radiotherapy. Until the mid 1990's the radiation therapy associated with BCT usually involved 5-7 weeks of daily treatment with external beam radiation delivered to the whole breast (during the last two-weeks of treatment a boost dose of radiation was typically delivered only to the tumor bed). The biologic argument for whole breast irradiation comes from various studies demonstrating that breast cancer is often multicentric.
Studies demonstrate that the logistic and temporal problems of scheduling 5-7 weeks of external beam radiation therapy (EBRT) have a substantial effect on patient's choice of treatment. As a result, in certain parts of the United States, as few as 10% of medically eligible patients receive BCT. Thus, even though breast-conserving surgery and EBRT have been proven to be equivalent to mastectomy in the management of women with early-stage breast carcinoma, this form of BCT has limited practicality. Additionally, it has not been definitively established how much of the clinically uninvolved breast tissue surrounding the lumpectomy cavity must be treated by radiation. Treatment of clinically uninvolved breast tissue with EBRT after lumpectomy is generally believed to play a significant role in the occurrence of acute and chronic toxicity associated with this form of BCT. Moreover, large retrospective reviews have shown that, in certain subsets of patients with early-stage breast cancer, incidence of failures outside the lumpectomy bed are rare, and the use of whole breast EBRT does not appear to significantly affect the incidence of failure outside the tumor bed.
In the face of these shortcomings of whole-breast EBRT, investigations were initiated to develop treatments that limit radiation treatment to the surgical bed plus a 10-20 mm margin of tissue circumferentially for the management of patients with early stage breast cancers who additionally satisfied certain medical eligibility criteria. Rationale for the new methodology also emphasized the delivery of larger doses of radiation per fraction to the lumpectomy cavity. This accelerated partial breast irradiation (APBI) therapy aims to preserve local control and cosmesis while decreasing the overall length of the treatment, and is typically completed for APBI in 5-7 days. The objective is to provide the breast conserving option to a larger population of women through offering a new method that is logistically simpler and more practical, and in prospective has reduced treatment related toxicities. APBI therapy addresses problems that are both side-effect and quality of life related.
Interstitial and Intracavitary APBI
Multicatheter-based interstitial brachytherapy was the focus of initial studies evaluating APBI therapy. It was used to treat the excision site plus an additional 10-20 mm margin of tissue. Follow-up data at a median of 6 years suggest that multicatheter-based APBI is comparable to whole-breast irradiation in both safety and efficacy. Despite encouraging clinical results, only a minority of institutions have adopted multicatheter-based interstitial brachytherapy. Apparently because the optimal outcome of the treatment requires extensive practitioner experience associated with both the complexity of the procedure and with the associated intricate and time-consuming treatment planning.
The MammoSite brachytherapy (MSB) applicator is one example of a new and potentially superior technology for APBI therapy, which is intended to deliver intracavitary radiation to the surgical margins after lumpectomy. The device is a double lumen balloon catheter that is surgically inserted into the tumor bed during a lumpectomy procedure or postlumpectomy during a separate open or ultrasonically guided closed procedure within 10 weeks of the surgery.
The balloon catheter is inflated with a saline/contrast mixture to fill the entire cavity. Conformance to the surrounding tissue is checked usually with a computed tomography (CT) scan. CT images are also used to ensure an absence of air pockets between the balloon and the surrounding tissue, as well as to measure the balloon diameter, symmetry, and proximity to the skin and chest wall. The balloon catheter may be used as a high-dose rate (HDR) brachytherapy applicator to deliver intracavitary highly conformal radiation to the surgical margins plus typically an additional 10 mm of tissue surrounding the tumor bed to include clinically unapparent microscopic disease beyond the resection margins.
The MSB applicator simplifies delivery of HDR breast brachytherapy. First Phase I and II trials have already demonstrated that the device performs well clinically and provides improved dose coverage and reproducibility compared to interstitial implantation, as well as being easy to implant.
Success and Limitations of MSB
Eighty-seven institutions and 1,419 patients with stage 0, I, or II breast carcinoma who were undergoing breast conserving therapy were enrolled in a trial designed to collect data on the clinical use of the MammoSite breast brachytherapy catheter for delivering breast irradiation from May 4, 2002 through Jul. 30, 2004. The MSB device was placed in 1,403 of these patients. The MSB catheter demonstrated acceptable technical reproducibility between multiple institutions and use in appropriate groups of patients in delivering APBI. Cosmetic results at 12 months (92% good/excellent) were comparable to those reported for whole-breast radiation therapy. Early toxicity rates (infections, radiation recall) appeared acceptable. The recommended radiation dose fractionation scheme was 34 Gray (Gy) delivered at a point 10 mm from the surface of the balloon in 3.4 Gy fractions (twice daily separated by a minimum of 6 hrs) over 5 to 7 elapsed days with various commercially available, remote HDR after-loaders.
Skin Spacing—Correlation to Cosmesis:
The results of the MSB catheter trial described above confirmed previous observations that early cosmesis is related strongly to skin spacing. At 12 months, 96% of patients had a good/excellent cosmetic result with skin spacing ≧7 mm. 86% of patients with <7 mm of skin spacing had a good/excellent cosmetic result, suggesting that other factors (area/volume of tissue receiving higher doses) may impact on the ultimate cosmetic result. In 12% of patients with <7 mm of skin spacing, significant radiation effects were readily observable, and 2% had severe sequelae of breast tissue secondary to radiation effects. One of the technical eligibility criteria for participation in this trial was minimum applicator-to-skin distance of 5 mm. Explantation of the device due to inadequate balloon-to-skin distance was an overwhelming 35% of all explanted patients (3.1% overall).
Another recent study has analyzed factors associated with the cosmetic outcome achieved using the MSB applicator to treat patients with partial breast irradiation. The study population comprised 30 patients. 53.3% of the patients were reported to have an excellent cosmetic outcome and 40% had a good cosmetic outcome. The mean maximal skin doses per fraction in the excellent and good outcome groups were 354.8 cGy and 422.3 cGy, respectively. Excellent cosmetic outcome was also associated with a greater balloon-to-skin distance.
Approximately 130,000 women are candidates for BCT in the United States each year. Since the MSB treatment system's FDA approval in 2002, over 22,000 patients have been treated with this procedure. It has again been noted that the skin-balloon surface distance and balloon-cavity conformance were the main factors limiting the initial use of the MammoSite applicator. As the use of the MSB treatment system grows, it is estimated that this limitation may effect as many as 4,000 patients each year.
Radiation Recall Reactions—Skin Spacing, Chemotherapy:
Radiation recall reaction is usually broadly referring to the generalized development of a significant skin reaction (erythema, dry/moist desquamation) approximately 37 weeks after the completion of radiation therapy. Thus, both a delayed effect of radiation therapy on the skin and a redevelopment of a skin reaction secondary to the administration of radiosensitizing drugs are referred to as radiation recall reactions. It is believed that this effect is enhanced by the concurrent use of certain systemic chemotherapy agents. Adriamycin radiation recall dermatitis has been associated with external beam radiation therapy for 30 years, for example.
Development of a radiation recall reaction was evaluated in the Registry Trial on clinical use of the MSB described above, and of 442 patients that were evaluated for radiation recall reaction, 74 of these patients had received chemotherapy. A recall reaction was developed in 13.5% of patients who received chemotherapy (10 patients) versus only 1.4% (5 patients) who did not receive chemotherapy. Thus, patients who received concurrent chemotherapy were more likely to experience a recall reaction, suggesting that, in some patients, the early use of systemic chemotherapy agents can exacerbate or precipitate this reaction. Out of the 15 patients who developed a recall reaction, 3 had skin spacing <7 mm (6% of 50 patients with <7 mm skin spacing) versus 12 of 392 patients (3%) who had skin spacing >7 mm. Thus, again, patients with smaller skin spacing more frequently experienced a recall reaction (without chemotherapy).
If future studies confirm with higher certainty the association of radiation recall reaction after APBI therapy with adjuvant chemotherapy, some precautions will need to be considered. These safety measures may include 1) the delayed start of chemotherapy, 2) avoidance of certain radiosensitizing drugs, or 3) use only in patients with greater skin spacing.
Clinical Target Volume and MSB:
As already mentioned, the precise amount of clinically uninvolved tissue that must be included within the high-dose volume has not yet been definitively established. During multicatheter interstitial brachytherapy the amount of uninvolved tissue treated is an additional 10-20 mm circumferentially to the lumpectomy cavity. Three-dimensional conformal radiation therapy (3DCRT) is a relatively new and less invasive form of APBI. 3DCRT employs multiple noncoplanar beams to provide a relatively more focused dose of radiation to the excision cite plus, again, a 10-20 mm margin.
Earlier studies with the MSB applicator have included up to an additional 15 mm of tissue circumferentially. However, therapy protocols that are currently used in everyday practice include only 10 mm of clinically uninvolved tissue. Limiting factors potentially include the dose to portions of the heart and lung, but the principal dose-limiting factor for MSB is the dose to the overlying skin. Thus, a major consideration for a somewhat reduced size of the circumferentially treated tissue during MSB is not yet established clinically or scientifically, but is dictated by risk management of significant skin reactions. Yet, some studies have documented microscopic spread beyond 20 mm from the edge of the gross tumors in 29% of women with extensive intraductal component-negative breast cancers.
Improvements to the above procedures would increase overall effective treatment.